4-6270040-G-GGCGCGGTGGCTGTGGGCA
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1
The NM_006005.3(WFS1):c.-6+32_-6+49dupGTGGCTGTGGGCAGCGCG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,020 control chromosomes in the GnomAD database, including 4,631 homozygotes. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.21 ( 4630 hom., cov: 29)
Exomes 𝑓: 0.081 ( 1 hom. )
Consequence
WFS1
NM_006005.3 intron
NM_006005.3 intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -1.74
Genes affected
WFS1 (HGNC:12762): (wolframin ER transmembrane glycoprotein) This gene encodes a transmembrane protein, which is located primarily in the endoplasmic reticulum and ubiquitously expressed with highest levels in brain, pancreas, heart, and insulinoma beta-cell lines. Mutations in this gene are associated with Wolfram syndrome, also called DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness), an autosomal recessive disorder. The disease affects the brain and central nervous system. Mutations in this gene can also cause autosomal dominant deafness 6 (DFNA6), also known as DFNA14 or DFNA38. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP6
Variant 4-6270040-G-GGCGCGGTGGCTGTGGGCA is Benign according to our data. Variant chr4-6270040-G-GGCGCGGTGGCTGTGGGCA is described in ClinVar as [Benign]. Clinvar id is 1233567.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
WFS1 | NM_006005.3 | c.-6+32_-6+49dupGTGGCTGTGGGCAGCGCG | intron_variant | Intron 1 of 7 | ENST00000226760.5 | NP_005996.2 | ||
WFS1 | NM_001145853.1 | c.-2+32_-2+49dupGTGGCTGTGGGCAGCGCG | intron_variant | Intron 1 of 7 | NP_001139325.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.212 AC: 32117AN: 151824Hom.: 4612 Cov.: 29
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GnomAD4 exome AF: 0.0814 AC: 7AN: 86Hom.: 1 Cov.: 0 AF XY: 0.106 AC XY: 7AN XY: 66
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GnomAD4 genome AF: 0.212 AC: 32172AN: 151934Hom.: 4630 Cov.: 29 AF XY: 0.208 AC XY: 15482AN XY: 74260
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Jul 15, 2018
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at